The present invention relates to the composition of giant ring compounds and methods for preparing the giant ring compounds.
Phospholipids, a major constituent of biological membranes, typically possess two chains of 14-18 carbons each of which are linked to the glycerol backbone by means of ester functionalities. Such compounds are stable at ambient temperature and neutral pH, but readily decompose at: elevated temperatures; in highly acidic media; and/or in enzymatic reactions catalyzed by esterases. Furthermore, since the hydrophobic chains are connected only at one end, they have a certain amount of freedom within the membrane bilayer to wiggle, bend, and interdigitate.
It has been observed that thermophilic archaebacteria are fully functional at temperatures up to 90.degree. C. and some at external pH values as low as 0.5. The ability of these bacteria to thrive under such adverse conditions is believed to be due in part to the unique lipids present in the plasma membrane. Two of the unique features of lipids of the plasma membrane being that they are macrocyclic and have a complete absence of ester linkages. The lack of ester linkages results in enhanced stability of such lipids to enzymatic hydrolysis by esterases, in addition to the temperature and pH stability. The cyclic nature of the lipids from archaebacteria is characterized as long isoprenoid chains bound through ether linkages to two polar heads; the two polar heads being either two glycerols or one glycerol and one nonitol. See, for example, Rosa et al., J.C.S. Chem. Comm. 514-515 (1977); Yamauchi et al., Biochim. Biophy. Acta 1003, 151-160 (1989); Yamauchi et al., J. Am. Chem. Soc. 112, 3188-3191 (1990).
Due to the unique properties of the lipids from archaebacteria, there is interest in using such lipids to form thermal, enzymatic, and pH stable membranes as liposomes for drug and pesticide delivery, for use in cleaning products, and for use in high performance fluids such as high temperature lubricants. However, it is difficult to obtain the bacterial lipids from natural sources and chemical synthesis is not an easy task.
Synthetic procedures for making macrocyclic rings having 12 to 20 atoms in the backbone of the ring include a method for preparing ether-linked phospholipids based on regiospecific opening of glycidyl derivatives mediated by boron trifluoride as described by Guivisdalsky et al. J. Org. Chem. 54, 4637-4642 (1989).
Yamauchi et al. J. Am. Chem. Soc. 112, 3188-3191 (1990) describe the synthesis of 1,1'-(1,32-dotriacontamethylene)-bis-(2-phytanyl-sn-glycero-3-phosphocholi ne) as a model to study the macrocyclic lipids.
McMurry et al. J. Am. Chem. Soc. 112, 6942-6949 (1990) describe a process for forming macrocyclic diols having a 14-membered carbocyclic ring. None of the procedures currently used have been effective in preparing macrocyclic lipids having greater than 12 to 20 atoms in the ring in significant yields.
It would therefore be advantageous to synthetically produce macrocycles having greater than 20 atoms in the backbone of the ring whereby the hydrophobic chains are linked to a polar backbone. It would also be advantageous to have macrocycles of greater than 20 atoms where the hydrophobic chains are linked to a glycerol backbone by means of ether functionalities. Such macrocycles have enhanced thermal stability, chemical stability, photolytic stability and enzymatic stability compared to previously synthesized cyclic stuctures which contain ester linkages.